As genetic engineering progresses, humanity will be faced with issues of morality time and time again. Splice looks at the field of artificial life and the specific issue of combining human and non-human DNA. In the film, two researchers, facing the loss of their research, decide to combine human and animal DNA to create a new life form - just to prove it can be done. Once the birth occurs, each has a different response to the creature and those responses change over time as Dren develops towards adulthood.

The plot focuses on the different relationships Clive and Elsa have to the being they have birthed for science. Fearing their employer's response, they hide Dren and eventually mover her off site to protect her. Dren's development affects both scientists in different ways, with each responding to Dren and each other in different and sometimes horrific ways.